A Study to Evaluate the Differences in Pharmadynamics, Pharmacokinetics, and Safety Between Ciprofol and Propofol

NCT04294056 | Completed Phase 1

• 1 other identifier: HSK3486-109
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open-label, randomized, two-stage, two-way crossover Phase I study in healthy male subjects.The main objective is to evaluate the differences in pharmadynamics (PD), pharmacokinetics (PK), and safety between ciprofol injectable emulsion and propofol injectable emulsion at different doses in healthy subjects.

Conditions

Anesthesia

Outcome Measures

Primary Outcomes (3)

• Modified observer's assessment of alertness/sedation（MOAA/S）

  Observe the change of modified observer's assessment of alert /sedation during the whole trial

  From first dose of study drug until fully alert on day 1

• Bispectral index （BIS）

  From first dose of study drug until fully alert on day 1

• Safety by measurement of Adverse Events

  First dose of study drug on day 1

Secondary Outcomes (7)

• Peak concentration (Cmax)

  First dose of study drug on day 1

• Area under the plasma concentration versus time curve (AUC)

  First dose of study drug on day 1

• Terminal half-life (t1/2)

  First dose of study drug on day 1

• time to peak concentration (Tmax)

  First dose of study drug on day 1

• clearance (CL)

  First dose of study drug on day 1

Other Outcomes (2)

• Use of dynamometer to estimate Muscular strength of lower limbs

  From 30 minutes before administration to 1 hour after administration on day 1

• The differences between the Montreal Cognitive Assessment (MoCA) test score in Ciprofol group and in a control group of Propofol

  From the baseline period to 1 hour after administration on day 1

Study Arms (2)

Ciprofol

EXPERIMENTAL

First-stage: 0.4mg/kg, 0.6 mg/kg, 0.8 mg/kg Second-stage: 0.4mg/kg, 0.6 mg/kg, 0.8 mg/kg

Drug: Ciprofol

Propofol

ACTIVE COMPARATOR

First-stage: 2.0mg/kg, 3.0 mg/kg, 4.0 mg/kg Second-stage: 2.0mg/kg, 3.0 mg/kg, 4.0 mg/kg

Drug: Propofol

Interventions

Ciprofol DRUG

First-stage: 0.4mg/kg, 0.6 mg/kg, 0.8 mg/kg Second-stage: 0.4mg/kg, 0.6 mg/kg, 0.8 mg/kg

Ciprofol

Propofol DRUG

First-stage: 2.0mg/kg, 3.0 mg/kg, 4.0 mg/kg Second-stage: 2.0mg/kg, 3.0 mg/kg, 4.0 mg/kg

Propofol

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult males, aged 18-45 years (inclusive);
• Body weight ≥ 50 kg, body mass index (BMI) between 18-26 kg/m\^2 (inclusive);
• Blood pressure between 90-140/50-90 mmHg (inclusive); heart rate between 60-100 bpm (inclusive); body temperature between 35.4-37.5°C (inclusive); respiratory rate between 12-20 breaths per min (inclusive); SpO2 when inhaling ≥ 92%;
• Normal results of physical examination, laboratory tests (routine blood, routine urine, blood biochemistry (including hepatic function, renal function, blood glucose, and electrolytes such as Na, K, and Mg), and blood coagulation), 12-lead ECG, and abdominal ultrasonography, or abnormalities considered by the investigators to be clinically insignificant; no significant potential difficult airway (modified Mallampati score Class I-II);
• No previous history of primary diseases in major organs, such as liver, kidneys, digestive tract, blood, and metabolic diseases; no history of malignant hyperthermia and other hereditary disorders; no history of mental/neurological disorders; no history of epilepsy; no contraindications for deep sedation/general anesthesia; no clinically significant history of anesthesia accidents;
• Subjects must understand the procedures and methods of this study, and be willing to signing the informed consent form and to complete the trial in strict accordance with clinical trial protocol;

You may not qualify if:

• Patients with known allergies to ciprofol injectable emulsion, excipient in propofol injectable emulsion (soybean oil, glycerin, triglyceride, egg lecithin, sodium oleate, and sodium hydroxide); history of drug allergies (including other anesthetics), allergic diseases, or hyperactive immune response;
• Patients receiving any of the following drugs or therapies prior to screening/administration:
• History of drug abuse within 3 months prior to screening, or positive result in urine drug screening during baseline period;
• Participated in other drug/medical device trials within 3 month prior to screening;
• Serious infection, trauma, or major surgery within 4 weeks prior to screening.
• Acute disease with clinical significance (determined by the investigators) within 2 weeks prior to screening, including GI diseases or infections (such as respiratory tract or CNS infections);
• Patients who received propofol, other sedatives/anesthetics, and/or opioid analgesics within 1 week prior to administration;
• Patients who received prescription drugs, Chinese herbal medicines, over-the-counter drugs, or food supplements (such as vitamins and calcium supplements) other than contraceptives, paracetamol, oral non-steroidal anti-inflammatory drugs, and topical over-the-counter preparations, within 2 weeks prior to administration; those who received UGT or CYP2B6 inhibitors within 7 days prior to administration (refer to Attachment 6 for prohibited drugs); patients can only be enrolled when the principal investigator (PI) and the sponsor agree that the medication has no effect on the safety and PK/PD results of the trial;
• Patients with history or evidence of any of the following diseases prior to screening/administration:
• History of cardiovascular diseases, such as postural hypotension, severe arrhythmia, heart failure, Adams-Stokes syndrome, unstable angina, myocardial infarction within 6 months before screening, tachycardia/bradycardia requiring medications, third-degree atrioventricular block, or QTcF interval ≥ 450 ms (per Fridericia's correction formula);
• Subjects with hypopnea, history of obstructive pulmonary disease, history of asthma, or sleep apnea syndrome; subjects with history of failed endotracheal intubation; history of bronchospasm requiring interventions within 3 months prior to screening; acute upper respiratory tract infection within 1 week prior to baseline, with symptoms such as fever, wheeze, nasal obstruction, or cough;
• History of gastrointestinal disorders: history of gastrointestinal retention, active hemorrhage, or conditions that may lead to reflux and aspiration;
• Laboratory results meeting any of the following during screening/at baseline:
• Positive result for any of the markers, including HBsAg, HCV-Ab, HIV-Ab, and Tp-Ab;
• Results for hepatic and renal functions exceeding the following ranges:

Sponsors & Collaborators

• Haisco Pharmaceutical Group Co., Ltd.: lead

Study Sites (1)

Sichuan Provincial People's Hospital

Chengdu, China

Location

MeSH Terms

Interventions

(2-(1R)-1-cyclopropyl)ethyl-6-isopropyl-phenol; Propofol

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2020
• First Posted: March 3, 2020
• Study Start: May 26, 2020
• Primary Completion: June 22, 2020
• Study Completion: September 18, 2020
• Last Updated: November 20, 2020

Record last verified: 2020-02

Locations

CN (1)