A Study Evaluating the Drug-Drug Interaction Between KL0011034 Injection and Alfentanil Hydrochloride Injection

Official title

A Single-Center, Randomized, Open-Label, Three-Sequence, Three-Period Crossover Study to Evaluate the Drug-Drug Interaction Between KL0011034 Injection and Alfentanil Hydrochloride Injection

Overview

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

• Drug KL0011034 injection
  Intravenous injection, single dose
• Drug Alfentanil Hydrochloride Injection
  Intravenous injection, single dose

Primary outcome measures

• Number of reported Adverse Events [Time frame: 24 hours post-dose for each period]

Secondary outcome measures (9)

• PK parameter Cmax in plasma [Time frame: 24 hours post-dose for each period]
• PK parameter Tmax in plasma [Time frame: 24 hours post-dose for each period]
• PK parameter AUC0-t in plasma [Time frame: 24 hours post-dose for each period]
• PK parameter AUC0-∞ in plasma [Time frame: 24 hours post-dose for each period]
• PK parameter t1/2 in plasma [Time frame: 24 hours post-dose for each period]
• Modified Observer's Assessment of Alertness Sedation (MOAA/S) scale [Time frame: Day 1 for each period]
• Electroencephalogram bispectrality index (BIS) monitoring [Time frame: Day 1 for each period]
• Loss of eyelash reflex [Time frame: Day 1 for each period]
• Modified Aldrete Scoring (Aldrete) Scale [Time frame: Day 1 for each period]

Eligibility criteria

Inclusion criteria

• patients with moderate-to-severe non-cancerous chronic pain (Age: 18\~55 years, NRS score≥4);
• Body Weight: Male≥50.0kg, Female≥45.0kg; 19.0 ≤BMI≤ 26.0;
• There were no abnormalities in clinically significant physical examination, vital signs, 12-lead electrocardiogram, chest x-ray, abdominal B-ultrasound, laboratory tests;

Exclusion criteria

• Allergy or Drug hypersensitivity;
• Clinically significant Medical History;
• History of anesthesia accident, history of serious adverse reactions of anesthesia, or family history of anesthesia accidents, or contraindications to general anesthesia;
• Dyspnoea or suspected difficult airway, or predicting difficult endotracheal intubation;
• History of bronchial asthma, chronic obstructive pulmonary disease, sleep apnea syndrome;
• History of adrenal insufficiency or adrenal tumor or hereditary heme biosynthesis disorder or hereditary acute porphyria;
• History of any surgery within 3 months;
• History of any Medication within 14 days;
• History of any inducers or inhibitors of CYP3A4 or CYP2C19 enzymes within 30 days;
• History of any clinical study within 3 months;
• History of any vaccine within 1 month;
• History of any drug abuse;
• Needle sickness, Hematosickness;
• Massive blood loss (> 400 mL) in the past 3 months;
• Female volunteers are pregnant or lactating;
• History of unprotected sex within 2 weeks;
• Heavy smoker ( more than 5 cigarettes/day) within 3 months;
• History of alcohol abuse,or heavy alcohol intake (more than 14 units a week) within 6 months;
• Heavy caffeine intake;
• History of grapefruit, xanthine-rich foods intake within 48 hours;
• Positive alcohol test;
• Positive nicotine test;
• Positive drugs of abuse test result.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Third XIANGYA Hospital of Central South University — Changsha

Identifiers

NCT: NCT07710560 · KL0011034-102

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗