Danavorexton in healthy volunteers receiving an opioid
| ISRCTN | ISRCTN63027076 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN63027076 |
| EudraCT/CTIS number | 2021-003869-35 |
| Secondary identifying numbers | TAK-925-1021 |
- Submission date
- 13/04/2022
- Registration date
- 20/04/2022
- Last edited
- 02/02/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English Summary
Background and study aims
Danavorexton is a new compound that is central to the control of arousal and wakefulness. Clinical studies with sleep-deprived healthy volunteers and patients with sleep disorders have demonstrated that danavorexton administered into a vein was well-tolerated and improved wakefulness. The aim of this study is to assess the safety, tolerability, pharmacokinetics (how the body affects the drug), and pharmacodynamics (how the drug affects the body) of danavorexton in healthy volunteers undergoing opioid-induced respiratory depression (OIRD), and to assess the effect of danavorexton on OIRD. The information obtained from the present study may become beneficial to patients who have OIRD in the future.
Who can participate?
Healthy male volunteers aged 18 to 55 years
What does the study involve?
Participants will receive single low and high dose danavorexton or placebo (dummy drug) on two separate occasions.
What are the possible benefits and risks of participating?
The most common nonserious side effects (occurring in more than 5% of subjects) reported in clinical trials with danavorexton include the following: nausea or feeling like vomiting, increased blood pressure, and an increased need to urinate. These side effects were categorized as mild or moderate, and no serious side effects occurred in any participant. Participants may also experience side effects from remifentanil which will be used to induce OIRD. Some side effects of remifentanil include: blurred vision, chest pain, confusion, dizziness or feeling lightheaded when getting up, irregular breathing (too fast or too slow), irregular heartbeat, chest pain, muscle stiffness, sweating or unusual tiredness. There are no direct benefits from participating.
Where is the study run from?
Leiden University Medical Center (Netherlands)
When is the study starting and how long is it expected to run for?
March 2021 to May 2022
Who is funding the study?
Takeda (USA)
Who is the main contact?
ademhalingsonderzoek@lumc.nl
Contact information
Principal Investigator
Albinusdreef 2
Leiden
2333 ZA
Netherlands
| Phone | +31 (0)715262301 |
|---|---|
| a.dahan@lumc.nl |
Study information
| Study design | Single-center randomized double-blind placebo-controlled crossover trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A randomized, double-blind, placebo-controlled, two-way crossover, Phase I study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of danavorexton in healthy subjects undergoing opioid-induced respiratory depression |
| Study acronym | TAK-925-1021 |
| Study hypothesis | The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of danavorexton in healthy subjects undergoing opioid-induced respiratory depression (OIRD) as well as to assess the effect of danavorexton on OIRD. |
| Ethics approval(s) | Approved 26/01/2022, Stichting BEBO (Dr. Nassaulaan 10, 9401 HK Assen, Netherlands; +31 (0)592 40 58 71; info@stbebo.nl), ref: not applicable |
| Condition | Opioid-induced respiratory depression |
| Intervention | Participants will receive sequentially single intravenous (IV) low- and high-dose danavorexton or placebo on two separate occasions. On study days 1 and 3, participants will stay at the hospital for several hours after each infusion has completed and will be monitored to ensure they are stable post-opioid and TAK-925 infusions. They can then be discharged home. After day 3 there is a virtual follow up on day 9 but no further planned in-person visits. Dosages cannot be disclosed as per sponsor requirements. Randomization is performed by a designee of the sponsor prior to the start of the study. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Danavorexton |
| Primary outcome measure | 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 | 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: 1. Observed plasma concentration at the end of infusion (Ceoi) 2. Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast) 3. Area under the plasma concentration-time curve from time 0 to infinity (AUC∞) |
| Overall study start date | 25/03/2021 |
| Overall study end date | 20/05/2022 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Male |
| Target number of participants | 16 |
| Total final enrolment | 13 |
| Participant 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 (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 |
| Participant exclusion criteria | 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 |
| Recruitment start date | 10/03/2022 |
| Recruitment end date | 08/05/2022 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Leiden
2333ZA
Netherlands
Sponsor information
Industry
Hayden Avenue 95
Lexington
MA 02421
United States of America
| Phone | +1 (0)510 7402412 |
|---|---|
| medical@mlnm.com | |
| Website | http://www.takeda.com/ |
"ROR" |
https://ror.org/03bygaq51 |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Takeda, Takeda Pharmaceuticals U.S.A., Inc., Takeda Pharmaceutical Company Limited, Takeda Pharmaceuticals America, Inc., Takeda in the U.S., TPUSA
- Location
- United States of America
Results and Publications
| Intention to publish date | 20/04/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | Separate data sharing agreements will be set up in case someone is requesting the data. Please contact Prof. Albert Dahan (a.dahan@lumc.nl). |
Editorial Notes
02/02/2023: The following changes were made to the trial record:
1. The overall trial end date was changed from 01/06/2022 to 20/05/2022.
2. The intention to publish date was changed from 01/08/2022 to 20/04/2023.
3. Total final enrolment added.
20/04/2022: Trial's existence confirmed by Stichting BEBO.
