Chronic Pain
Conditions
Keywords
chronic pain
Brief summary
To evaluate the pharmacokinetic interaction of KL0011034 injection in combination with alfentanil hydrochloride injection.To evaluate the safety and tolerability of KL0011034 injection in combination with alfentanil hydrochloride injection.To evaluate the effect of alfentanil hydrochloride injection on the pharmacodynamics of KL0011034 injection.
Detailed description
This study will be conducted among the participants with moderate-to-severe non-cancerous chronic pain, aiming to evaluate the drug-drug interactions between KL0011034 injection and alfentanil hydrochloride injection. The study consists of two parts: Part 1 trial: A single-center, randomized, open, parallel design is adopted to evaluate the safety, tolerability and pharmacodynamic characteristics of the combined use of KL0011034 injection and alfentanil hydrochloride injection. It is planned to enroll 9 patients with moderate-to-severe non-cancerous chronic pain. All participants will be randomly assigned to one of the three dose groups in a 1:1:1 ratio, with 3 participants in each group. They will complete a single combined administration and undergo pharmacodynamic and safety evaluations. Based on the results of Part 1 trial, KL0011034 injection will select the maximum dose with acceptable safety among the three doses for the second part of the study. Part 2 trial: A single-center, randomized, open, three-sequence, three-period crossover trial design is adopted to evaluate the PK interactions, safety and tolerability of the combined use of KL0011034 injection and alfentanil hydrochloride injection, as well as the effect of alfentanil hydrochloride injection on the pharmacodynamics of KL0011034 injection. It is planned to enroll 18 patients with moderate-to-severe non-cancerous chronic pain. All participants will be randomly assigned to one of the three sequences A, B, and C in a 1:1:1 ratio, with 6 participants in each sequence. They will complete three periods of open administration and undergo PK blood sampling, pharmacodynamic and safety evaluations, with a 3-day washout period for each period.
Interventions
Intravenous injection, single dose
Intravenous injection, single dose
Sponsors
Hunan Kelun Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. patients with moderate-to-severe non-cancerous chronic pain (Age: 18\~55 years, NRS score≥4); 2. Body Weight: Male≥50.0kg, Female≥45.0kg; 19.0 ≤BMI≤ 26.0; 3. There were no abnormalities in clinically significant physical examination, vital signs, 12-lead electrocardiogram, chest x-ray, abdominal B-ultrasound, laboratory tests;
Exclusion criteria
1. Allergy or Drug hypersensitivity; 2. Clinically significant Medical History; 3. History of anesthesia accident, history of serious adverse reactions of anesthesia, or family history of anesthesia accidents, or contraindications to general anesthesia; 4. Dyspnoea or suspected difficult airway, or predicting difficult endotracheal intubation; 5. History of bronchial asthma, chronic obstructive pulmonary disease, sleep apnea syndrome; 6. History of adrenal insufficiency or adrenal tumor or hereditary heme biosynthesis disorder or hereditary acute porphyria; 7. History of any surgery within 3 months; 8. History of any Medication within 14 days; 9. History of any inducers or inhibitors of CYP3A4 or CYP2C19 enzymes within 30 days; 10. History of any clinical study within 3 months; 11. History of any vaccine within 1 month; 12. History of any drug abuse; 13. Needle sickness, Hematosickness; 14. Massive blood loss (\> 400 mL) in the past 3 months; 15. Female volunteers are pregnant or lactating; 16. History of unprotected sex within 2 weeks; 17. Heavy smoker ( more than 5 cigarettes/day) within 3 months; 18. History of alcohol abuse,or heavy alcohol intake (more than 14 units a week) within 6 months; 19. Heavy caffeine intake; 20. History of grapefruit, xanthine-rich foods intake within 48 hours; 21. Positive alcohol test; 22. Positive nicotine test; 23. Positive drugs of abuse test result.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of reported Adverse Events | 24 hours post-dose for each period | Safety and tolerability was assessed by the number of volunteers with adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameter Cmax in plasma | 24 hours post-dose for each period | Maximum peak plasma concentration (Cmax) of KL0011034 and its metabolite combining with or without Alfentanil Hydrochloride Injection. Cmax of Alfentanil combining with or without KL0011034 injection. |
| PK parameter Tmax in plasma | 24 hours post-dose for each period | Time of Cmax (Tmax) of KL0011034 and its metabolite combining with or without Alfentanil Hydrochloride Injection. Tmax of Alfentanil combining with or without KL0011034 injection. |
| PK parameter AUC0-t in plasma | 24 hours post-dose for each period | Area under the concentration-time curve (AUC0-t) from time zero to time "t" of KL0011034 and its metabolite combining with or without Alfentanil Hydrochloride Injection. AUC0-t of Alfentanil combining with or without KL0011034 injection. |
| PK parameter AUC0-∞ in plasma | 24 hours post-dose for each period | AUC from time zero to infinity (AUC0-∞) of KL0011034 and its metabolite combining with or without Alfentanil Hydrochloride Injection. AUC0-∞ of Alfentanil combining with or without KL0011034 injection. |
| PK parameter t1/2 in plasma | 24 hours post-dose for each period | Terminal-phase elimination half-life (t1/2) of KL0011034 and its metabolite combining with or without Alfentanil Hydrochloride Injection. t1/2 of Alfentanil combining with or without KL0011034 injection. |
| Modified Observer's Assessment of Alertness Sedation (MOAA/S) scale | Day 1 for each period | MOAA/S is a commonly used clinical sedation assessment scale, ranging from 0 to 5, which helps clinicians determine the level of sedation in patients. A score of 5 indicates full consciousness, whereas a score of 0 indicates deep coma. Lower scores correspond to deeper levels of sedation. |
| Electroencephalogram bispectrality index (BIS) monitoring | Day 1 for each period | BIS is the most widely used method for the continuous monitoring of sedation depth in clinical anesthesia. BIS values range from 0 to 100, where 100 represents complete wakefulness and 0 indicates complete cortical electrical inhibition. |
| Loss of eyelash reflex | Day 1 for each period | The eyelash reflex is a commonly used clinical method to assess the level of consciousness in patients. Gentle stimulation of the eyelashes with a cotton swab normally elicits a blink; absence of this response indicates loss of the eyelash reflex. |
| Modified Aldrete Scoring (Aldrete) Scale | Day 1 for each period | The Modified Aldrete Score is the most widely used standardized tool for assessing discharge readiness from post-anesthesia care unit (PACU). It evaluates five parameters: activity, respiration, blood pressure consciousness, and SpO₂. Ranging from 0 to 10, the higher the score, the better the quality of recovery. |
Countries
China
Outcome results
None listed