Drug-drug Interaction Study of KL1333 in Healthy Subjects

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

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

Study Overview

• Status: Completed
• Conditions: Mitochondrial Disease
• Intervention / Treatment: Drug: KL1333; Drug: Flurbiprofen; Drug: Dextromethorphan; Drug: Bupropion; Drug: Midazolam injection; Drug: Omeprazole; Drug: Caffeine; Drug: Repaglinide

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 Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom
    • Volunteer recruitment center Covance Leeds Covance Leeds

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females, of any race, between 18 and 65 years of age, inclusive.
2. Weight ≥50 kg and body mass index between 18.0 and 32.0 kg/m2, inclusive.
3. 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.
4. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception as detailed in Appendix 4.
5. Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
6. Able to perform all protocol-specified assessments and comply with the study visit schedule.

Exclusion Criteria:

1. 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.
2. 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.
3. History of gastroesophageal reflux disease, gastric erosions, peptic ulcer disease, or gastrointestinal bleeding episodes.
4. 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).
5. 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.
6. History of clinically significant illness or surgery within 4 weeks prior to screening, as determined by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Abliva AB

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2020
• Primary Completion (Actual): December 17, 2020
• Study Completion (Actual): December 17, 2020

Study Registration Dates

• First Submitted: November 13, 2020
• First Submitted That Met QC Criteria: November 18, 2020
• First Posted (Actual): November 25, 2020

Study Record Updates

• Last Update Posted (Actual): October 20, 2021
• Last Update Submitted That Met QC Criteria: October 19, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Mitochondrial Diseases; Hypoglycemic Agents; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Purinergic Antagonists; Purinergic Agents; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Respiratory System Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Dopamine Uptake Inhibitors; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Antitussive Agents; Midazolam; Bupropion; Dextromethorphan; Caffeine; Omeprazole; Flurbiprofen; Repaglinide
• Other Study ID Numbers: KL1333 2020-103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No