Drug-drug Interaction Study of KL1333 in Healthy Subjects

Study Overview
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Brief Summary
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A Phase I, Open-label, Fixed-sequence, Crossover, Drug-drug Interaction Study to Investigate the Inhibition Potential of KL1333 on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in Healthy Subjects

Detailed Description
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This will be a Phase I, open-label, fixed-sequence, crossover study to investigate the effect of coadministration of KL1333 on the PK of repaglinide, caffeine, omeprazole, midazolam, bupropion, dextromethorphan, and flurbiprofen in healthy male and female subjects. Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to the first dose administration. Subjects will be admitted into the clinical research unit (CRU) on Day -1 and be confined to the CRU until discharge on Day 19. Subjects will return to the CRU for a follow-up visit 5 to 7 days after the last dose.

Official Title
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A Phase I, Open-label, Fixed-sequence, Crossover, Drug-drug Interaction Study to Investigate the Inhibition Potential of KL1333 on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in Healthy Subjects

Conditions
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Mitochondrial Disease

Intervention / Treatment
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* Drug: KL1333
* Drug: Flurbiprofen
* Drug: Dextromethorphan
* Drug: Bupropion
* Drug: Midazolam injection
* Drug: Omeprazole
* Drug: Caffeine
* Drug: Repaglinide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, of any race, between 18 and 65 years of age, inclusive. Weight ≥50 kg and body mass index between 18.0 and 32.0 kg/m2, inclusive. In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhaemolytic hyperbilirubinaemia [eg, suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at screening and check-in as assessed by the investigator. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception as detailed in Appendix 4. Able to comprehend and willing to sign an ICF and to abide by the study restrictions. Able to perform all protocol-specified assessments and comply with the study visit schedule. Exclusion Criteria: Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, including KL1333 or its excipients, unless approved by the investigator. History of gastroesophageal reflux disease, gastric erosions, peptic ulcer disease, or gastrointestinal bleeding episodes. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs including cholecystectomy (uncomplicated appendectomy and hernia repair will be allowed). History of malignancy of any organ system other than localised basal cell carcinoma of the skin, treated or untreated, within 5 years prior to screening, regardless of whether there is evidence of local recurrence or metastases. History of clinically significant illness or surgery within 4 weeks prior to screening, as determined by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Crossover Assignment
Interventional Model Description: All subjects are treated in the same arm, but in a crossover manner.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Daily treatment | Drug: KL1333<br>* Tablet<br>Drug: Flurbiprofen<br>* Tablet<br>Drug: Dextromethorphan<br>* Syrap<br>Drug: Bupropion<br>* Tablet<br>Drug: Midazolam injection<br>* solution for injection<br>* Other names: Midazolam;Drug: Omeprazole<br>* Capsule<br>Drug: Caffeine<br>* Tablet or capsule<br>Drug: Repaglinide<br>* Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of the effect of KL1333 on the PK of repaglinide, caffeine, omeprazole, midazolam, bupropion, dextromethorphan, and flurbiprofen in healthy subjects. | Area under the curve AUC | day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluation of the single-dose PK of repaglinide, caffeine, omeprazole, midazolam, bupropion, dextromethorphan, and flurbiprofen administered alone and in the presence of KL1333 in healthy subjects | Area under the curve AUC | Day 14 | 
| assessment of the safety and tolerability of KL1333 when coadministered with repaglinide, caffeine, omeprazole, midazolam, bupropion, dextromethorphan, and flurbiprofen in healthy subjects. | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). | Day 14 |