Study for Evaluating the Efficacy of Ciprofol in Patients Under Narcotic Sleep With Chronic Insomnia

Study Overview
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Brief Summary
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This is a single center, randomized, single blind, exploratory clinical study.About 30 patients with chronic insomnia are planned to be enrolled in this study and randomized into two groups by a ratio of 4:1 (Figure 1), with group 1 (24 subjects) for ciprofol and group 2 (6 subjects) for placebo (fat emulsion). Cognitive behavioral therapy (CBT) will be given to these patients during the treatment.

Official Title
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A Single Center, Randomized, Single Blind, Exploratory Study for Evaluating the Efficacy of Ciprofol in Patients Under Narcotic Sleep With Chronic Insomnia

Conditions
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Chronic Insomnia

Intervention / Treatment
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* Drug: ciprofol
* Drug: medium/long chain fat emulsion injection (C8-24Ve)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18 (inclusive) to 70 (inclusive) years old; ASA class of I-II; With chronic insomnia refractory to conventional drugs in the past 3 months (benzodiazepine receptor agonists and other drugs). Other drugs: melatonin, melatonin receptor agonists, and traditional Chinese medicine; Compliant with the diagnostic criteria of ICSD-3 chronic insomnia: At least one of the following chief complaints: initial insomnia, difficulty in sleep maintenance, early awakening, refusal to go to bed at an appropriate time, and difficulty in falling asleep without nursing; At least one of the following daytime symptoms: tiredness, short tempered, work/study/social skills decreased; Occurrence of the above symptoms at least 3 times per week and lasting for more than 3 months; Voluntarily adopt narcotic sleep and obtain the written informed consent form. Exclusion Criteria: With contraindications to deep sedation/general anesthesia or a history of past sedation/anesthesia accidents; With a history of allergy or contraindications to anesthetics; With a medical history or evidence of any of the followings before screening/at baseline, which may increase sedation/anesthesia risks: History of cardiovascular diseases: uncontrolled hypertension [systolic blood pressure (SBP) ≥ 170 mmHg and/or diastolic blood pressure (DBP) ≥ 105 mmHg without treatment, or SBP > 160 mmHg and/or DBP > 100 mmHg despite antihypertensive treatment], severe arrhythmia, heart failure, Adams-stokes syndrome, New York Heart Association (NYHA) Class ≥ III, severe superior vena cava syndrome, pericardial effusion, acute myocardial ischemia, unstable angina, myocardial infarction within 6 months before screening, history of tachycardia/bradycardia requiring medical treatment, II-III degree atrioventricular block (excluding patients with pacemakers); History of respiratory system disorders: respiratory insufficiency, history of obstructive pulmonary disease, history of bronchospasm requiring treatment within 3 months before screening, and acute respiratory tract infection with obvious symptoms such as fever, wheezing, nasal obstruction, and cough within 1 week before baseline; History of neurological and psychiatric disorders: craniocerebral injury, possible convulsions, myoclonus, intracranial hypertension, cerebral aneurysms, history of cerebrovascular accidents; schizophrenia, mania, insanity, history of cognitive disorder; history of epilepsy; mental disorder suggested by Mini International Neuropsychiatric Interview (MINI); History of gastrointestinal disorders: gastrointestinal retention, active hemorrhage, or conditions that may lead to reflux and aspiration; History of blood donation or blood loss of ≥ 400 mL within 3 months before screening; With the following airway management risks at screening: History of asthma or stridor; Sleep apnea syndrome; History or family history of malignant hyperthermia; History of tracheal intubation failure; Judged by investigators to have difficult airway or judged as difficult tracheal intubation (modified Mallampati class IV) at screening; Receipt of any of the following medications/therapies at screening/baseline: Any clinical study within 1 month before screening; Sedatives/anesthetics, and/or sedative-hypnotics within 72 h before baseline; Antidepressants and anxiolytics within 14 days before baseline; Laboratory test abnormalities at screening: Total bilirubin > 2 × ULN (upper limit of normal); Aspartate aminotransferase (AST) and alanine transaminase (ALT) > 2 × ULN; Blood creatinine > 1.5 × ULN; Unable to fast for 6 h before dose administration; With a history of smoking, drug abuse and/or positive urine drug screening results, or positive breath alcohol test results at baseline and/or a history of alcohol abuse within 3 months before screening. Alcohol abuse is defined as an average of > 2 units of alcohol consumed per day (1 unit = 360 mL of beer with 5% alcohol, 45 mL of liquor with 40% alcohol, or 150 mL of wine); Pregnant or breastfeeding females; women of child-bearing potential or men who are unwilling to use contraception during the trial; or patients who are planning pregnancy within 1 month after the trial (including male patients); Unable to avoid engaging in dangerous occupations requiring concentration and/or motor coordination 72 h after administration; Judged by investigators to be unsuitable for participating in this trial for any reason.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ciprofol<br> | Drug: ciprofol<br>* intravenous infusion of ciprofol at 0.12 mg/kg, followed by 0.4-1.6 mg/kg/h for maintenance<br>|
| Placebo Comparator: placebo<br> | Drug: medium/long chain fat emulsion injection (C8-24Ve)<br>* at the infusion rate of 25-30 mL/h<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Polysomnography (PSG) | total sleep time (TST) | Day -2 to Day 90 | 
| Polysomnography (PSG) | sleep latency (SL) | Day -2 to Day 90 | 
| Polysomnography (PSG) | wake after sleep onset (WASO) | Day -2 to Day 90 | 
| Sleep log | subjective total sleep time (sTST) | Day -2 to Day 90 | 
| Sleep log | subjective sleep-onset latency (sSOL) | Day -2 to Day 90 | 
| Sleep log | subjective wake after sleep onset (sWASO) | Day -2 to Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-rating scales | Pittsburgh Sleep Quality Index (PSQI)（0-21） | Day -2 to Day 90 | 
| Self-rating scales | Insomnia Severity Index (ISI)（0-28） | Day -2 to Day 90 | 
| Self-rating scales | PHQ-9 Depression Test Questionnaire（0-27） | Day -2 to Day 90 | 
| Self-rating scales | GAD-7 Anxiety Test Questionnaire（0-21） | Day -2 to Day 90 | 
| Self-rating scales | Epworth Somnolence Scale（0-24）; | Day -2 to Day 90 |