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A Study to Evaluate the Drug-Drug Interaction Between KL0011034 Injection and Alfentanil Hydrochloride Injection in Participants With Moderate-to-Severe Non-Cancer Chronic Pain

3 agosto 2026 aggiornato da: Guoping Yang, The Third Xiangya Hospital of Central South University

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 in Trial Participants With Moderate-to-Severe Non-Cancer Chronic Pain

This study will evaluate the drug-drug interaction between KL0011034 Injection and Alfentanil Hydrochloride Injection in participants with moderate-to-severe non-cancer chronic pain. The study consists of two parts. Part 1 is a single-center, randomized, open-label, parallel-design study to evaluate the safety, tolerability, and pharmacodynamics of the combination. Approximately 9 participants will be enrolled and randomized to one of three dose groups (n=3 per group). Part 2 is a single-center, randomized, open-label, three-sequence, three-period crossover study to evaluate the pharmacokinetic interaction, safety, tolerability, and pharmacodynamic effects. Approximately 18 participants will be enrolled and randomized to one of three sequences (n=6 per sequence), with a 3-day washout period between each period.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Study Design and Population:

This is a two-part, single-center, randomized, open-label study in participants with moderate-to-severe non-cancer chronic pain. Part 1 uses a parallel-group design, and Part 2 uses a three-sequence, three-period crossover design.

Part 1 (Safety, Tolerability, and Pharmacodynamics):

Approximately 9 participants will be randomized in a 1:1:1 ratio to one of three dose groups to receive a single combined dose of Alfentanil Hydrochloride Injection 5 μg/kg plus KL0011034 Injection at one of three dose levels (Group 1: 0.3 mg/kg; Group 2: 0.35 mg/kg; Group 3: 0.4 mg/kg). Pharmacodynamic and safety evaluations will be conducted, and participants will be discharged after the end-of-study examinations on Day 2 (D2). Based on the results from Part 1, the maximum dose of KL0011034 Injection among the three dose levels that is deemed safe and tolerable will be selected for use in Part 2.

Part 2 (Pharmacokinetic Interaction, Safety, Tolerability, and Pharmacodynamics):

Approximately 18 participants will be randomized in a 1:1:1 ratio to one of three sequences (A, B, or C), with 6 participants per sequence. Each participant will complete three open-label treatment periods (Day 1, Day 4, and Day 7), with a 3-day washout period between periods. The selected KL0011034 dose from Part 1 will be used in Part 2. Pharmacokinetic sampling, pharmacodynamic evaluations, and safety assessments will be performed during each period. Participants will be discharged after the end-of-study examinations on Day 8 (D8).

Sequence A: Period 1: KL0011034 Injection (selected dose); Period 2: Alfentanil Hydrochloride Injection 5 μg/kg; Period 3: Alfentanil Hydrochloride Injection 5 μg/kg + KL0011034 Injection (selected dose).

Sequence B: Period 1: Alfentanil Hydrochloride Injection 5 μg/kg; Period 2: Alfentanil Hydrochloride Injection 5 μg/kg + KL0011034 Injection (selected dose); Period 3: KL0011034 Injection (selected dose).

Sequence C: Period 1: Alfentanil Hydrochloride Injection 5 μg/kg + KL0011034 Injection (selected dose); Period 2: KL0011034 Injection (selected dose); Period 3: Alfentanil Hydrochloride Injection 5 μg/kg.

Tipo di studio

Interventistico

Iscrizione (Stimato)

27

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto

Accetta volontari sani

Sì

Descrizione

Inclusion Criteria:

  1. Those who fully understand the purpose, content, process and possible risks of the trial, and voluntarily participate and sign the informed consent form;
  2. Male and female patients with moderate to severe non-cancerous chronic pain (such as patients with shoulder inflammation, chronic back pain, myofascial pain syndrome) aged between 18 and 55 years (inclusive of the boundary values), with a NRS score of >= 4;
  3. Male weight not less than 50.0 kg, female weight not less than 45.0 kg; Body Mass Index (BMI) within the range of 19.0 to 26.0 kg/m2 (including the critical value);
  4. From the date of signing the informed consent form to the last administration of the trial medication within 3 months, the trial participants (and their partners) have no plans for conception, and the trial participants have no plans for sperm donation/egg donation; From the date of signing the informed consent form to the completion of the exit examination, the participants voluntarily adopt non-pharmacological contraceptive measures; After the exit examination to the last 3 months after the last administration of the trial medication, the participants voluntarily adopt effective contraceptive measures;
  5. Able to communicate well with the researchers, willing and able to comply with the lifestyle restrictions stipulated in the protocol, and cooperate to complete the trial process.

Exclusion Criteria:

  1. Known to be allergic to alfentanil or other opioid analgesics, etomidate or other anesthetic drugs, or to be of allergic constitution (such as allergy to two or more drugs, food or pollen), or prone to develop rashes, urticaria, etc., or having a history of allergic diseases, or known to be allergic to the excipients or raw materials of this product;
  2. Having a history of head trauma, possible intracranial hypertension, cerebral aneurysm, cerebrovascular accident, or mental illness such as schizophrenia, mania, bipolar disorder, mental confusion, long-term use of psychotropic drugs or cognitive dysfunction;
  3. Having a history of serious cardiovascular diseases (such as hypertension, heart failure, severe arrhythmia, etc.) and/or heart diseases, family history of heart disease and/or unstable angina pectoris, or having had a myocardial infarction in the past 6 months;
  4. Having a history of other cardiovascular, endocrine, respiratory, digestive, urinary, nervous, hematological and/or lymphatic system diseases, and the investigator considers that it still has clinical significance during the screening;
  5. Having a history of anesthesia accidents, severe adverse reactions during anesthesia or family history of anesthesia accidents, or having contraindications for general anesthesia;
  6. Having difficulty breathing or suspected difficult airway or estimated difficulty in tracheal intubation (such as modified Mallampati score grade III-IV, congenital small tongue, maldevelopment of mandible, etc.);
  7. Having a history of airway diseases such as bronchial asthma, chronic obstructive pulmonary disease, sleep apnea syndrome, etc.;
  8. Having a history of adrenal insufficiency, adrenal tumor or hereditary hemoglobin biosynthesis disorder or hereditary acute porphyria;
  9. Having a surgical history within 3 months before screening, or not recovering from surgery, or having planned surgery during the trial;
  10. Having conditions, surgical history, diseases related to the use of the test drug, or any other special circumstances that may significantly affect drug absorption, distribution, metabolism and excretion;
  11. Abnormal results of physical examination, vital signs, full thoracic radiograph, abdominal B-ultrasound, laboratory tests (blood routine, urine routine, blood biochemistry, coagulation function) have clinical significance;
  12. Having clinically significant electrocardiogram abnormalities found during screening, such as QTcF >=450 ms (male) or >=460 ms (female), etc.;
  13. Positive for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), and syphilis spirochete antibody (TP-Ab);
  14. Having unprotected sexual behavior within 2 weeks before the first administration of the test drug;
  15. Female subjects during the screening period are in pregnancy or lactation, or have a positive pregnancy result;
  16. Having a history of drug abuse or drug dependence within the past 1 year, or having a positive urine drug screening at the time of screening;
  17. Having a history of alcohol abuse within 6 months before screening [that is, consuming more than 14 standard units of alcohol per week (1 unit = 360 ml of beer or 45 ml of 40% alcohol liquor or 150 ml of wine)], or being unwilling to stop drinking alcohol or any alcoholic products during the trial, or having a positive alcohol breath test at the time of screening;
  18. Having a history of smoking within 3 months before screening (daily smoking quantity >= 5 cigarettes), or being unwilling to stop using any tobacco products during the trial, or having a positive smoke test result at the time of screening;
  19. Having consumed excessive (8 cups or more, 1 cup = 250 ml) tea, coffee or caffeine-containing beverages (such as milk tea, cola, etc.) every day within 14 days before screening, or being unwilling to stop drinking these beverages during the trial;
  20. Individuals who consumed grapefruit/grapefruit juice, foods or beverages rich in xanthine components (such as shiitake mushrooms, white carp, black carp, whelk, white bream, oysters, white snapper, sea eel, duck liver, chicken liver, pork intestines, pork liver, beef liver, etc.) within 48 hours before the first administration of the test drug, or those who had any special diet that could affect the absorption, distribution, metabolism, or excretion of the drug;
  21. Individuals who had used any medication within 14 days before the first administration of the test drug, including prescription drugs, over-the-counter drugs, traditional Chinese medicines, health supplements, and vitamins;
  22. Individuals who had used inhibitors or inducers of CYP3A4 or CYP2C19 (such as CYP3A4 inhibitors: sirivatinib, atalenti, edalizumab, telifast, clarithromycin, itraconazole, ketoconazole, posaconazole, voriconazole, indinavir, nelfinavir, ritonavir, sapparin, tipranavir, lopinavir, nafamoxin, cobizumet; CYP3A4 inducers: apalutamide, enzalutamide, rumactat, mitotane, evolizumab, phenytoin, carbamazepine, rifampicin, St. John's wort; CYP2C19 inhibitors: fluvoxamine, fluconazole, fluoxetine, ticlopidine, phenabarbital, nalfurafine, voriconazole; CYP2C19 inducers: rifampicin, apalutamide, efavirenz, enzalutamide, phenytoin) within 1 month before the first administration of the test drug;
  23. Individuals who had been using sedative drugs and/or opioid analgesics for more than 3 months before screening;
  24. Individuals who had participated in any clinical trials and used the test drug/medical device within 3 months before the first administration of the test drug, or were still in the follow-up period of other trials;
  25. Individuals who had received inactivated vaccines within 1 month before screening, or received live/deleted vaccines within 3 months before screening, or planned to receive inactivated/live/deleted vaccines during the trial;
  26. Individuals who had undergone blood loss or blood donation or transfusion or received a total amount of blood products exceeding 400 ml within 3 months before screening, or planned to donate blood or undergo surgery within 1 month after the trial or after the trial ends;
  27. Individuals with difficulty in blood collection, or those who cannot tolerate venipuncture, or those with a history of fainting or needle shock;
  28. Individuals with poor compliance, or other situations that the researcher deems unsuitable for participation in the study.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione incrociata
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 1.Alfentanil 5 µg/kg + KL0011034 0.3 mg/kg
Part 1: Participants receive a single dose of Alfentanil Hydrochloride Injection 5 μg/kg combined with KL0011034 Injection 0.3 mg/kg on Day 1. Safety, tolerability, and pharmacodynamic evaluations are conducted.
KL0011034 Injection is an investigational drug being studied for its analgesic properties in combination with alfentanil. It is administered via intravenous infusion. The dose levels evaluated are 0.3 mg/kg, 0.35 mg/kg, and 0.4 mg/kg in Part 1; the selected dose from Part 1 is used in Part 2.
Alfentanil Hydrochloride Injection is an opioid analgesic administered via intravenous bolus at a fixed dose of 5 μg/kg. It is used alone and in combination with KL0011034 Injection to evaluate drug-drug interaction.
Sperimentale: 2.Alfentanil 5 µg/kg + KL0011034 0.35 mg/kg
Part 1: Participants receive a single dose of Alfentanil Hydrochloride Injection 5 μg/kg combined with KL0011034 Injection 0.35 mg/kg on Day 1. Safety, tolerability, and pharmacodynamic evaluations are conducted.
KL0011034 Injection is an investigational drug being studied for its analgesic properties in combination with alfentanil. It is administered via intravenous infusion. The dose levels evaluated are 0.3 mg/kg, 0.35 mg/kg, and 0.4 mg/kg in Part 1; the selected dose from Part 1 is used in Part 2.
Alfentanil Hydrochloride Injection is an opioid analgesic administered via intravenous bolus at a fixed dose of 5 μg/kg. It is used alone and in combination with KL0011034 Injection to evaluate drug-drug interaction.
Sperimentale: 3.Alfentanil 5 µg/kg + KL0011034 0.4 mg/kg
Part 1: Participants receive a single dose of Alfentanil Hydrochloride Injection 5 μg/kg combined with KL0011034 Injection 0.4 mg/kg on Day 1. Safety, tolerability, and pharmacodynamic evaluations are conducted.
KL0011034 Injection is an investigational drug being studied for its analgesic properties in combination with alfentanil. It is administered via intravenous infusion. The dose levels evaluated are 0.3 mg/kg, 0.35 mg/kg, and 0.4 mg/kg in Part 1; the selected dose from Part 1 is used in Part 2.
Alfentanil Hydrochloride Injection is an opioid analgesic administered via intravenous bolus at a fixed dose of 5 μg/kg. It is used alone and in combination with KL0011034 Injection to evaluate drug-drug interaction.
Sperimentale: 4.Sequence A: KL0011034 → Alfentanil → Alfentanil + KL0011034
Part 2, Sequence A: Participants receive three interventions across three periods (Day 1, Day 4, Day 7) with a 3-day washout between periods: Period 1: KL0011034 Injection (selected dose from Part 1); Period 2: Alfentanil Hydrochloride Injection 5 μg/kg; Period 3: Alfentanil Hydrochloride Injection 5 μg/kg + KL0011034 Injection (selected dose from Part 1). Pharmacokinetic, pharmacodynamic, and safety evaluations are conducted.
KL0011034 Injection is an investigational drug being studied for its analgesic properties in combination with alfentanil. It is administered via intravenous infusion. The dose levels evaluated are 0.3 mg/kg, 0.35 mg/kg, and 0.4 mg/kg in Part 1; the selected dose from Part 1 is used in Part 2.
Alfentanil Hydrochloride Injection is an opioid analgesic administered via intravenous bolus at a fixed dose of 5 μg/kg. It is used alone and in combination with KL0011034 Injection to evaluate drug-drug interaction.
Sperimentale: 5. Sequence B: Alfentanil → Alfentanil + KL0011034 → KL0011034
Part 2, Sequence B: Participants receive three interventions across three periods (Day 1, Day 4, Day 7) with a 3-day washout between periods: Period 1: Alfentanil Hydrochloride Injection 5 μg/kg; Period 2: Alfentanil Hydrochloride Injection 5 μg/kg + KL0011034 Injection (selected dose from Part 1); Period 3: KL0011034 Injection (selected dose from Part 1). Pharmacokinetic, pharmacodynamic, and safety evaluations are conducted.
KL0011034 Injection is an investigational drug being studied for its analgesic properties in combination with alfentanil. It is administered via intravenous infusion. The dose levels evaluated are 0.3 mg/kg, 0.35 mg/kg, and 0.4 mg/kg in Part 1; the selected dose from Part 1 is used in Part 2.
Alfentanil Hydrochloride Injection is an opioid analgesic administered via intravenous bolus at a fixed dose of 5 μg/kg. It is used alone and in combination with KL0011034 Injection to evaluate drug-drug interaction.
Sperimentale: 6. Sequence C: Alfentanil + KL0011034 → KL0011034 → Alfentanil
Part 2, Sequence C: Participants receive three interventions across three periods (Day 1, Day 4, Day 7) with a 3-day washout between periods: Period 1: Alfentanil Hydrochloride Injection 5 μg/kg + KL0011034 Injection (selected dose from Part 1); Period 2: KL0011034 Injection (selected dose from Part 1); Period 3: Alfentanil Hydrochloride Injection 5 μg/kg. Pharmacokinetic, pharmacodynamic, and safety evaluations are conducted.
KL0011034 Injection is an investigational drug being studied for its analgesic properties in combination with alfentanil. It is administered via intravenous infusion. The dose levels evaluated are 0.3 mg/kg, 0.35 mg/kg, and 0.4 mg/kg in Part 1; the selected dose from Part 1 is used in Part 2.
Alfentanil Hydrochloride Injection is an opioid analgesic administered via intravenous bolus at a fixed dose of 5 μg/kg. It is used alone and in combination with KL0011034 Injection to evaluate drug-drug interaction.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Maximum Plasma Concentration (Cmax) of KL0011034
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours
Cmax of KL0011034 in plasma, determined by non-compartmental analysis of concentration-time data.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours
Maximum Plasma Concentration (Cmax) of KL0011034 Metabolite A644S(A)-Z7
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Cmax of KL0011034 major metabolite A644S(A)-Z7 in plasma, determined by non-compartmental analysis of concentration-time data.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Maximum Plasma Concentration (Cmax) of Alfentanil
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Cmax of Alfentanil in plasma, determined by non-compartmental analysis of concentration-time data.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) of KL0011034
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours
AUC0-t of KL0011034 in plasma, determined by non-compartmental analysis using linear-log trapezoidal method.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) of KL0011034 Metabolite A644S(A)-Z7
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours
AUC0-t of KL0011034 major metabolite A644S(A)-Z7 in plasma, determined by non-compartmental analysis using linear-log trapezoidal method.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) of Alfentanil
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours
AUC0-t of Alfentanil in plasma, determined by non-compartmental analysis using linear-log trapezoidal method.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours
Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of KL0011034
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours
AUC0-∞ of KL0011034 in plasma, calculated as AUC0-t + Clast/λz.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours
Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of KL0011034 Metabolite A644S(A)-Z7
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours
AUC0-∞ of KL0011034 major metabolite A644S(A)-Z7 in plasma, calculated as AUC0-t + Clast/λz.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours
Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Alfentanil
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing);immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours
AUC0-∞ of Alfentanil in plasma, calculated as AUC0-t + Clast/λz.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing);immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Time to Maximum Plasma Concentration (Tmax) of KL0011034
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Tmax of KL0011034 in plasma, determined directly from concentration-time data.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Time to Maximum Plasma Concentration (Tmax) of KL0011034 Metabolite A644S(A)-Z7
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Tmax of KL0011034 major metabolite A644S(A)-Z7 in plasma, determined directly from concentration-time data.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Time to Maximum Plasma Concentration (Tmax) of Alfentanil
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Tmax of Alfentanil in plasma, determined directly from concentration-time data.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Area Under the Curve From Time Zero to 24 Hours (AUC0-24h) of KL0011034
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
AUC0-24h of KL0011034 in plasma, determined by non-compartmental analysis.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Area Under the Curve From Time Zero to 24 Hours (AUC0-24h) of KL0011034 Metabolite A644S(A)-Z7
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
AUC0-24h of KL0011034 major metabolite A644S(A)-Z7 in plasma, determined by non-compartmental analysis.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Area Under the Curve From Time Zero to 24 Hours (AUC0-24h) of Alfentanil
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
AUC0-24h of Alfentanil in plasma, determined by non-compartmental analysis.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Elimination Half-Life (t1/2) of KL0011034
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Elimination half-life (t1/2) of KL0011034 in plasma, calculated as ln(2)/λz, where λz is the terminal elimination rate constant determined by log-linear regression of the terminal phase of the concentration-time curve. Unit: hours.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Elimination Half-Life (t1/2) of KL0011034 Metabolite A644S(A)-Z7
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Elimination half-life (t1/2) of KL0011034 major metabolite A644S(A)-Z7 calculated as ln(2)/λz, where λz is the terminal elimination rate constant determined by log-linear regression of the terminal phase.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Elimination Half-Life (t1/2) of Alfentanil
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Elimination half-life (t1/2) of Alfentanil calculated as ln(2)/λz, where λz is the terminal elimination rate constant determined by log-linear regression of the terminal phase.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Apparent Volume of Distribution (Vd) of KL0011034
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Apparent volume of distribution (Vd) of KL0011034 calculated as Dose/(AUC0-∞ × λz).
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Apparent Volume of Distribution (Vd) of KL0011034 Metabolite A644S(A)-Z7
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Apparent volume of distribution (Vd) of KL0011034 major metabolite A644S(A)-Z7 calculated as Dose/(AUC0-∞ × λz).
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Apparent Volume of Distribution (Vd) of Alfentanil
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Apparent volume of distribution (Vd) of Alfentanil calculated as Dose/(AUC0-∞ × λz).
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Clearance (CL) of KL0011034
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Total body clearance (CL) of KL0011034 calculated as Dose/AUC0-∞.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Clearance (CL) of KL0011034 Metabolite A644S(A)-Z7
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Total body clearance (CL) of KL0011034 major metabolite A644S(A)-Z7 calculated as Dose/AUC0-∞.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Clearance (CL) of Alfentanil
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Total body clearance (CL) of Alfentanil calculated as Dose/AUC0-∞.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Terminal Elimination Rate Constant (λz) of KL0011034
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Terminal elimination rate constant (λz) of KL0011034 determined by log-linear regression of the terminal phase of the concentration-time curve.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Terminal Elimination Rate Constant (λz) of KL0011034 Metabolite A644S(A)-Z7
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Terminal elimination rate constant (λz) of KL0011034 major metabolite A644S(A)-Z7 determined by log-linear regression of the terminal phase of the concentration-time curve.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Terminal Elimination Rate Constant (λz) of Alfentanil
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Terminal elimination rate constant (λz) of Alfentanil determined by log-linear regression of the terminal phase of the concentration-time curve.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Mean Residence Time (MRT0-∞) of KL0011034
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Mean residence time (MRT0-∞) of KL0011034 calculated as AUMC/AUC0-∞.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Mean Residence Time (MRT0-∞) of KL0011034 Metabolite A644S(A)-Z7
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Mean residence time (MRT0-∞) of KL0011034 major metabolite A644S(A)-Z7 calculated as AUMC/AUC0-∞.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after infusion completion, and at 2, 5, 10, 15, 20, 30, 40, 50 minutes, and 1, 2, 4, 8, 12, 24 hours post-dose.
Mean Residence Time (MRT0-∞) of Alfentanil
Lasso di tempo: Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Mean residence time (MRT0-∞) of Alfentanil calculated as AUMC/AUC0-∞.
Part 2, each of the 3 treatment periods (Day 1, Day 4, Day 7): pre-dose (within 60 minutes before dosing); immediately after bolus completion, and at 1, 2, 3, 6, 11, 16, 21, 31, 41, 51, 61 minutes, and 2, 4, 8, 12, 24 hours post-dose.
Adverse Events and Serious Adverse Events
Lasso di tempo: From signing of informed consent through study completion (up to Day 8 in Part 2); unresolved AEs followed every 2 weeks until resolution or stabilization, up to 28 days after last dose.
Incidence, severity, and causality of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) assessed by clinical observation and participant reporting.
From signing of informed consent through study completion (up to Day 8 in Part 2); unresolved AEs followed every 2 weeks until resolution or stabilization, up to 28 days after last dose.
Vital Signs
Lasso di tempo: Part 2: Screening, Day -1, pre-dose on Day 3 and Day 6, pre-dose and at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose in each treatment period (Day 1, Day 4, Day 7), and on Day 8 (end-of-study).
Change from baseline in vital signs including blood pressure, pulse rate, respiratory rate, tympanic temperature, and oxygen saturation (SpO2).
Part 2: Screening, Day -1, pre-dose on Day 3 and Day 6, pre-dose and at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose in each treatment period (Day 1, Day 4, Day 7), and on Day 8 (end-of-study).
12-Lead Electrocardiogram Parameters
Lasso di tempo: Part 2: Screening, Day -1, pre-dose on Day 3 and Day 6, pre-dose and at 30 minutes, 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose in each treatment period (Day 1, Day 4, Day 7), and on Day 8 (end-of-study).
Change from baseline in 12-lead ECG parameters including heart rate, PR interval, QRS interval, and QT interval corrected using Fridericia's formula (QTcF).
Part 2: Screening, Day -1, pre-dose on Day 3 and Day 6, pre-dose and at 30 minutes, 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose in each treatment period (Day 1, Day 4, Day 7), and on Day 8 (end-of-study).
Physical Examination
Lasso di tempo: Part 2: Screening, Day -1, and Day 8 (end-of-study).
Number of participants with clinically significant abnormalities in physical examination findings (skin, mucous membranes, lymph nodes, head, neck, chest, abdomen, spine/extremities, and nervous system), assessed by standard physical examination.
Part 2: Screening, Day -1, and Day 8 (end-of-study).
Injection Site Reactions
Lasso di tempo: Part 2: Pre-dose, immediately post-dose plus 30 seconds, and at 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, and 6 hours post-dose in each treatment period (Day 1, Day 4, and Day 7).
Incidence and severity of injection site reactions (pain, tenderness, erythema, and induration/swelling), assessed by physical examination of the injection site using a standardized assessment scale. Severity graded as mild, moderate, or severe.
Part 2: Pre-dose, immediately post-dose plus 30 seconds, and at 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, and 6 hours post-dose in each treatment period (Day 1, Day 4, and Day 7).
MOAA/S Sedation Score
Lasso di tempo: Part 1 and Part 2: From pre-dose (-5 minutes) at 20 seconds, 40 seconds, 1 minute, 1 minute 20 seconds, 1 minute 40 seconds, 2 minutes, 2 minutes 20 seconds, 2 minutes 40 seconds, 3 minutes, and every minute thereafter until full recovery plus 10 minutes
Sedation level assessed using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. Sedation onset defined as first MOAA/S score ≤4; recovery defined as MOAA/S score of 5 on 3 consecutive assessments.
Part 1 and Part 2: From pre-dose (-5 minutes) at 20 seconds, 40 seconds, 1 minute, 1 minute 20 seconds, 1 minute 40 seconds, 2 minutes, 2 minutes 20 seconds, 2 minutes 40 seconds, 3 minutes, and every minute thereafter until full recovery plus 10 minutes
Bispectral Index (BIS) Monitoring
Lasso di tempo: Part 1 and Part 2: From pre-dose (-5 minutes) continuously until full recovery plus 10 minutes (recorded every 1 minute); up to 10 minutes post-dose for participants with no response.
Continuous BIS monitoring to assess depth of sedation/anesthesia. Anesthesia onset defined as first BIS value ≤60; duration of BIS between 40 and 60 is recorded.
Part 1 and Part 2: From pre-dose (-5 minutes) continuously until full recovery plus 10 minutes (recorded every 1 minute); up to 10 minutes post-dose for participants with no response.
Eyelash Reflex
Lasso di tempo: Part 1 and Part 2: From pre-dose (-5 minutes) every 15 seconds until eyelash reflex recovery, with minimum assessment up to 2 minutes post-dose; for participants with no loss of reflex within 5 minutes post-dose, evaluated every 15 seconds up to 5 minute
Time to loss of eyelash reflex and time to recovery of eyelash reflex after study drug administration.
Part 1 and Part 2: From pre-dose (-5 minutes) every 15 seconds until eyelash reflex recovery, with minimum assessment up to 2 minutes post-dose; for participants with no loss of reflex within 5 minutes post-dose, evaluated every 15 seconds up to 5 minute
Modified Aldrete Score for Discharge Readiness
Lasso di tempo: Part 1 and Part 2: From awakening, every 2 minutes until discharge criteria met (score ≥9 on 3 consecutive assessments); for participants with no response, starting at 10 minutes post-dose, every 2 minutes until discharge criteria met.
Recovery assessed using the Modified Aldrete Score (evaluating activity, respiration, blood pressure, consciousness, and SpO2). Discharge criteria met when score ≥9 on 3 consecutive assessments.
Part 1 and Part 2: From awakening, every 2 minutes until discharge criteria met (score ≥9 on 3 consecutive assessments); for participants with no response, starting at 10 minutes post-dose, every 2 minutes until discharge criteria met.

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Collaboratori

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

30 luglio 2026

Completamento primario (Stimato)

31 luglio 2027

Completamento dello studio (Stimato)

31 luglio 2027

Date di iscrizione allo studio

Primo inviato

6 luglio 2026

Primo inviato che soddisfa i criteri di controllo qualità

3 agosto 2026

Primo Inserito (Effettivo)

7 agosto 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

7 agosto 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

3 agosto 2026

Ultimo verificato

1 agosto 2026

Maggiori informazioni

Termini relativi a questo studio

Altri numeri di identificazione dello studio

  • KL0011034-102

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Descrizione del piano IPD

Individual participant data (IPD) will not be shared because this is a first-in-human or early-stage clinical trial involving a novel investigational drug. The data contain proprietary and confidential information that could compromise ongoing patent applications and future commercial development. Public data sharing at this stage may also violate our confidentiality agreements with the contract research organization (CRO) and regulatory authorities. Therefore, IPD sharing is not feasible until the drug receives market approval or the primary study results are fully published.

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .