A Trial to Evaluate the Effect of Delgocitinib on the Heart Rhythm of Healthy People

Study Overview
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Brief Summary
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The purpose of this trial is to investigate the effects of delgocitinib, taken as a capsule, on the heart rhythms of healthy people, compared to a placebo.

Detailed Description
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The trial will be performed in two parts. Part 1: Group 1 (dose 1 or placebo) and Group 2 (dose 2 or placebo) Part 2: Group 3 (dose 3 or placebo) and Group 4 (dose 4 or placebo) The doses in Part 2 may be adjusted depending on the results of Part 1. Participants will be screened within 28 days of their dose. Participants will stay in the clinic from Day -1 to Day 2 (1 day postdose) and will be dosed on Day 1. A follow up phone call will take place 2 week (±2 days) after dosing.

Official Title
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A Phase 1 Clinical Trial to Evaluate QTcF Prolongation and Proarrhythmic Potential of the Non Antiarrhythmic Drug Delgocitinib Following Oral Administration in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Delgocitinib capsule
* Drug: Placebo capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index of ≥18.0 and <30.0 kg/m2. In good health, as judged by the investigator based on: medical history, physical examination, vital sign assessment, clinical laboratory evaluations . ECG without any clinically relevant abnormal findings at both screening and baseline No history of additional risk factors for torsades de pointes (for example, heart failure, hypokalaemia, family history of long QT syndrome). Female subjects of childbearing potential and male subjects with a female partner of childbearing potential must be willing to use highlly effective methods of contraception. Exclusion Criteria: Any disorder which is not stable and could: Affect the safety of the subject throughout the trial. Influence the findings of the trial. Impede the subject's ability to complete the trial. Use of any medication known to prolong the QT/QTc interval within 3 months or 5 half-lives of the drug, whichever is longer, prior to randomisation. Any medications, including St. John's wort, known to chronically alter drug absorption or elimination processes within 30 days prior to dosing. Current use of combined hormone contraceptives or combined hormonal replacement therapy. Subjects who have smoked (use of any type of tobacco and nicotine containing products) within the last 3 months prior to screening. History of chronic alcohol or drug abuse within 12 months prior to screening. Receipt of any vaccine approved for SARS-CoV-2 within 4 weeks prior to baseline and/or 2 weeks after dose. Receipt of live, attenuated vaccines within 4 weeks prior to baseline.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Delgocitinib placebo capsule | Drug: Placebo capsule<br>* oral capsule<br>|
| Experimental: Active dose 1<br>Delgocitinib capsule (Dose 1) | Drug: Delgocitinib capsule<br>* oral capsule<br>|
| Experimental: Active dose 2<br>Delgocitinib capsule (Dose 2) | Drug: Delgocitinib capsule<br>* oral capsule<br>|
| Experimental: Active dose 3<br>Delgocitinib capsule (Dose 3) | Drug: Delgocitinib capsule<br>* oral capsule<br>|
| Experimental: Active dose 4<br>Delgocitinib capsule (Dose 4) | Drug: Delgocitinib capsule<br>* oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline QTcF (ΔQTcF) | Replicate electrocardiograms (ECGs) (10 ECG replicates) for the determination of ΔQTc interval will be extracted from the continuous digital 12-lead ECG recording | predose to 24 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Placebo-corrected change from baseline QTcF (ΔΔQTcF) | Replicate electrocardiograms (ECGs) (10 ECG replicates) for the determination of ΔΔQTc interval will be extracted from the continuous digital 12-lead ECG recording | predose to 24 hours postdose | 
| Change from baseline of Heart Rate (ΔHR) | Replicate electrocardiograms (ECGs) (10 ECG replicates) for the determination of ΔHR interval will be extracted from the continuous digital 12-lead ECG recording | predose to 24 hours postdose | 
| Placebo-corrected, change from baseline of Heart Rate (ΔΔHR) | Replicate electrocardiograms (ECGs) (10 ECG replicates) for the determination of ΔΔHR interval will be extracted from the continuous digital 12-lead ECG recording | predose to 24 hours postdose | 
| Change from baseline of Pulse Rate (ΔPR) | Measurement of PR will be performed manually from electrocardiograms (ECGs). | predose to 24 hourse postdose | 
| Placebo-corrected, change from baseline of Pulse Rate (ΔΔPR) | Measurement of PR will be performed manually from electrocardiograms (ECGs). | predose to 24 hours postdose | 
| Change from baseline of QRS interval (ΔQRS) | Measurement of QRS will be performed manually from electrocardiograms (ECGs). | predose to 24 hours postdose | 
| Placebo-corrected, change from baseline of QRS interval (ΔΔQRS) | Measurement of QRS will be performed manually from electrocardiograms (ECGs). | predose to 24 hours postdose | 
| Frequency of treatment emergent changes in T-wave morphology. | Measurement of T-wave morphology will be performed manually | predose to 24 hours postdose | 
| Frequency of treatment emergent changes in U-waves presence | Measurement of U-waves presence will be performed manually | predose to 24 hours postdose | 
| Categorical outliers for QTcF, HR, PR interval, and QRS duration. | Analysis perfomed for changes in categorical outlines based on treatment emergent adverse events. | predose to 24 hours post-dose | 
| Number of treatment emergent adverse events |  | dosing to day 15 |