A Double-blind, Randomized, placebo-controlled, 3-way crossover study to eValuate the single dose Effects of Intranasal eSketamine on saFety of on-road driving in healthy subjects(DRiVE SaFe)
- Conditions
- Treatment resistent depression10027946
- Registration Number
- NL-OMON40941
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 24
1. Subject must be a man or woman, 21 to 60 years of age, inclusive and in general good health.;2. Body mass index (BMI) (weight [kg]/height[m]2) between 18 and 30 kg/m2(inclusive), and body weight not less than 45 kg;3. Blood pressure (after the subject is supine for 5 minutes) between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic at Screening and predose on Day 1 of Period 1.;4. A 12-lead ECG consistent with normal cardiac conduction and function at Screening and predose on Day 1 of Period 1.;5. Comfortable with self-administration of intranasal medication and able to follow instructions provided.;6. Before randomization, a woman must be either: ;Not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for at least 12 months, or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level >40 IU/L); permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy. ;Of childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal foam/gel/film/cream/suppository orocclusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the vasectomized partner should be the sole partner for that subject); true abstinence (when this is in line with the preferred and usual lifestyle of the subject);Note: If the childbearing potential changes after start of the study (e.g., woman who is not heterosexually active becomes active) a woman must begin a highly effective method of birth control, as described above. ;7. A woman of childbearing potential must have a negative urine pregnancy test at Screening and predose on Day 1 of Period 1.;8. A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 3 months after receiving the last dose of study drug.;9. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a double-barrier method of birth control e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, during the study and for 3 months after receiving the last dose of study drug. All men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug.;10. Subject has a valid driving license for more than 3 years, has driven at least 5000 km in the past year and is driving a car regularly.;11. Normal visual acuity (corrected or uncorrected).;12. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.;13. Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study.
1. Subject has clinically significant liver or renal insufficiency; cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic(including cataplexy and cognitive impairment), hematologic,rheumatologic, psychiatric, or metabolic disturbances. A significant primary sleep disorder is exclusionary.;2. Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening, as deemed appropriate by the investigator.;3. Clinically significant abnormal physical examination, vital signs, or 12-lead ECG at screening or on Day 1 of Period 1, as deemed appropriate by the investigator;4. Anatomical or medical conditions that may impede delivery or absorption of study medication (e.g., undergone facial reconstruction, rhinoplasty, significant structural or functional abnormalities of the nose or upper airway; obstructions or mucosal lesions of the nostrils or nasal passages; undergone sinus surgery in the previous 2 years; or signs and symptoms of rhinitispredose on Day 1 of Period 1).;5. Has an abnormal or deviated nasal septum with any oneor more of the following symptoms: blockage of one or both nostrils, nasal congestion (especially 1-sided), frequent nosebleeds, frequent sinus infections, and at times has facial pain, headaches, and postnasal drip.;6. Subject has a current or prior diagnosis of psychosis/psychotic disorder.;7. History of drug or alcohol abuse disorder within the past 1 year of Screening, or a reason to believe a subject has such a history.;8. Positive test for alcohol or drugs of abuse (cannabinoids, opiates, cocaine, amphetamines, benzodiazepines, hallucinogens, or barbiturates)at Screening or on Day 1 of Period 1.;9. Current suicidal or homicidal ideation/intent/behavior.;10. Subject has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situof the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence).;11. Subject has known allergies, hypersensitivity, or intolerance toesketamine or its excipients (refer to IB)or mirtazapine.;12. Subject has contraindications to the use of esketamine or ketamine, per local prescribing information and/or IB.;13. Donated blood or blood products or had substantial loss of blood (more than 500mL) within 3 months before the first administration of study drug or intention to donate blood or blood products during the study.;14. Disallowed therapies: ;- Received a known potent inhibitor of CYP3A or CYP2B6 activity (e.g., erythromycin, clarithromycin, ketoconazole, or itraconazole) within 1 week or a period less than 5 times the drugs half-life; whichever is longer, before the first dose of the study drug is scheduled.;- Received a potent inducer of CYP3A activity (e.g., rifampin) within 1 month before first dose of study drug is scheduled.;- Use of any prescription or nonprescription medication, within 14 days before the first scheduled dose of the study drug (including vitamins and herbal supplements; vasoconstrictors and decongestants that are administered by the ophthalmic or intranasal routes), except paracetamol, ibuprofen and oral contraceptives.;15. Subject has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 90 days, or 10 half-lives, whichever is longer, before the planned fi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Mean difference of standard deviation of lateral position (SDLP) from an onroad<br /><br>driving test.</p><br>
- Secondary Outcome Measures
Name Time Method <p>1. To evaluate the subjective driving performance of the subjects after the<br /><br>driving test.<br /><br>2. To evaluate sleepiness using the Karolinska Sleepiness Scale (KSS).<br /><br>3. To investigate the safety and tolerability of intranasal esketamine in<br /><br>healthy subjects, with<br /><br>special attention to:<br /><br>a. Effects on suicidal ideation/behavior measured by the Columbia Suicide<br /><br>Severity Rating Scale (C-SSRS);<br /><br>b. Psychosis-like side effects by using a four-item positive symptom subscale<br /><br>of the BPRS+ consisting of: suspiciousness/persecution, hallucinations, unusual<br /><br>thought content, and conceptual disorganization;<br /><br>c. Effects on dissociative symptoms using the CADSS;<br /><br>4. To evaluate the potential relationship between changes in driving<br /><br>performance, other PD and safety parameters and the Cmax of esketamine or<br /><br>noresketamine.</p><br>