Drug-drug Interaction Study of KL1333 in Healthy Subjects

Sponsor

Abliva AB (Industry)

Overall Status

Completed

CT.gov ID

NCT04643249

Collaborator

(none)

Enrollment

Location

Arm

1.2

Actual Duration (Months)

11.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Mitochondrial Disease	Drug: KL1333 Drug: Flurbiprofen Drug: Dextromethorphan Drug: Bupropion Drug: Midazolam injection Drug: Omeprazole Drug: Caffeine Drug: Repaglinide	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

N/A

Intervention Model:

Crossover Assignment

Intervention Model Description:

All subjects are treated in the same arm, but in a crossover manner.All subjects are treated in the same arm, but in a crossover manner.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Actual Study Start Date :

Nov 10, 2020

Actual Primary Completion Date :

Dec 17, 2020

Actual Study Completion Date :

Dec 17, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Daily treatment	Drug: KL1333 Tablet Drug: Flurbiprofen Tablet Drug: Dextromethorphan Syrap Drug: Bupropion Tablet Drug: Midazolam injection solution for injection Other Names: Midazolam Drug: Omeprazole Capsule Drug: Caffeine Tablet or capsule Drug: Repaglinide Tablet

Arm

Intervention/Treatment

Experimental: Active

Daily treatment

Drug: KL1333

Tablet

Drug: Flurbiprofen

Tablet

Drug: Dextromethorphan

Syrap

Drug: Bupropion

Tablet

Drug: Midazolam injection

solution for injection

Other Names:

Midazolam

Drug: Omeprazole

Capsule

Drug: Caffeine

Tablet or capsule

Drug: Repaglinide

Tablet

Outcome Measures

Primary Outcome Measures

Determination of the effect of KL1333 on the PK of repaglinide, caffeine, omeprazole, midazolam, bupropion, dextromethorphan, and flurbiprofen in healthy subjects. [day 14]
Area under the curve AUC

Secondary Outcome Measures

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 [Day 14]
Area under the curve AUC
assessment of the safety and tolerability of KL1333 when coadministered with repaglinide, caffeine, omeprazole, midazolam, bupropion, dextromethorphan, and flurbiprofen in healthy subjects. [Day 14]
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.