A Study to Evaluate the Effect of Intravenous (IV) Infusions of Risankizumab on Pharmacokinetics of Cytochome P450 Substrates in Adult Participants With Moderately to Severely Active Ulcerative Colitis or Crohn's Disease

Study Overview
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Brief Summary
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Ulcerative colitis (UC) is a type of inflammatory bowel disease that causes inflammation and bleeding from the lining of the rectum and colon (large intestine).Crohn's disease (CD) is a long-lasting condition causing inflammation that can affect any part of the gut. CD may cause tiredness, loose stools with or without bleeding, abdominal pain, weight loss, and fever. This study will evaluate the effect of repeated infusions of risankizumab on the pharmacokinetics of sensitive probe substrates of Cytochrome P450 (CYP) enzymes in participants with moderately to severely active UC or CD. Risankizumab is an investigational drug being developed to treat trial participants with inflammatory diseases such as UC and CD. The study is split into two periods. In Period 1, participants will receive single oral doses of CYP sensitive probes and in Period 2, participants will receive risankizumab followed by single oral doses of CYP sensitive probes. Around 20 adult participants with moderately to severely active CD or UC will be enrolled in the study across multiple sites worldwide. In Period 1, participants will receive oral doses of CYP sensitive probes on Day 1. In Period 2, participants will receive risankizumab by intravenous (IV) infusion on Days 1, 29 and 57 followed by oral CYP sensitive probes on Day 64. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests and checking for side effects.

Official Title
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A Phase 1 Study to Evaluate the Effect of Multiple IV Infusions of Risankizumab on the Pharmacokinetics of Cytochrome P450 Substrates Administered Orally in Subjects With Moderately to Severely Active Ulcerative Colitis or Crohn's Disease

Conditions
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Ulcerative Colitis (UC), Crohn's Disease

Intervention / Treatment
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* Drug: Risankizumab
* Drug: Cytochrome P450 (CYP) Substrates


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of UC or CD for at least 3 months prior to Day -1 (baseline). Appropriate documentation of biopsy results consistent with the diagnosis of CD or UC, in the assessment of the gastroenterologist, must be available. Moderately to severely active CD or UC. Must have demonstrated intolerance or inadequate response to one or more of the following categories of drugs: aminosalicylates, oral locally acting steroids, systemic steroids, immunomodulators, and/or approved biologic therapies. Participant must agree to not use any known inhibitors or inducers of cytochrome P450 within 1 month or 5 half-lives, whichever is greater before each administration of the cocktail probe and until the last pharmacokinetic sample is collected, 7 days after the intake of each probe cocktail. Exclusion Criteria: History of any clinically significant sensitivity or allergy to any medication or food. History of or active medical condition(s) or surgical procedure(s) that might affect gastrointestinal motility, pH, or absorption (e.g., celiac disease, gastroparesis, cholecystectomy, vagotomy). Positive for COVID-19 infection signs and symptoms.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cytochrome P450 (CYP) + Risankizumab<br>In Period 1, participants will receive single oral dose of Cytochrome P450 (CYP) substrates on Day 1. In Period 2, three IV doses of risankizumab on Days 1, 29 and 57, followed by single oral dose of CYP substrates on Day 64 will be administered. | Drug: Risankizumab<br>* Intravenous (IV) infusion<br>* Other names: ABBV-066;Drug: Cytochrome P450 (CYP) Substrates<br>* Tablet: Oral; CYP Substrates: midazolam, caffeine, warfarin, vitamin K, omeprazole and metoprolol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Midazolam | Maximum observed plasma concentration (Cmax) of Midazolam | Up to 71 Days | 
| Time to Maximum Observed Plasma Concentration (Tmax) of Midazolam | Time to maximum plasma concentration (Tmax) of Midazolam | Up to 71 Days | 
| Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Midazolam | Area Under the Plasma Concentration-time Curve (AUC) from time 0 to time of the last measurable concentration | Up to 71 Days | 
| AUC From Time 0 to Infinity (AUCinf) of Midazolam | Area Under the Plasma Concentration-time Curve (AUC) from time 0 to infinity | Up to 71 Days | 
| Terminal Phase Elimination Rate Constant (β) of Midazolam | Terminal phase elimination rate constant (β) for Midazolam | Up to 71 Days | 
| Terminal Phase Elimination Half-Life (t1/2) of Midazolam | Terminal phase elimination half-life (t1/2) of Midazolam | Up to 71 Days | 
| Maximum Observed Plasma Concentration (Cmax) of Caffeine | Maximum observed plasma concentration (Cmax) of Caffeine | Up to 71 Days | 
| Time to Maximum Observed Plasma Concentration (Tmax) of Caffeine | Time to maximum plasma concentration (Tmax) of Caffeine | Up to 71 Days | 
| Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Caffeine | Area Under the Plasma Concentration-time Curve (AUC) from time 0 to time of the last measurable concentration | Up to 71 Days | 
| AUC From Time 0 to Infinity (AUCinf) of Caffeine | Area Under the Plasma Concentration-time Curve (AUC) from time 0 to infinity | Up to 71 Days | 
| Terminal Phase Elimination Rate Constant (β) of Caffeine | Terminal phase elimination rate constant (β) for Caffeine | Up to 71 Days | 
| Terminal Phase Elimination Half-Life (t1/2) of Caffeine | Terminal phase elimination half-life (t1/2) of Caffeine | Up to 71 Days | 
| Maximum Observed Plasma Concentration (Cmax) of Warfarin | Maximum observed plasma concentration (Cmax) of Warfarin | Up to 71 Days | 
| Time to Maximum Observed Plasma Concentration (Tmax) of Warfarin | Time to maximum plasma concentration (Tmax) of Warfarin | Up to 71 Days | 
| Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Warfarin | Area Under the Plasma Concentration-time Curve (AUC) from time 0 to time of the last measurable concentration | Up to 71 Days | 
| AUC From Time 0 to Infinity (AUCinf) of Warfarin | Area Under the Plasma Concentration-time Curve (AUC) from time 0 to infinity | Up to 71 Days | 
| Terminal Phase Elimination Rate Constant (β) of Warfarin | Terminal phase elimination rate constant (β) for Warfarin | Up to 71 Days | 
| Terminal Phase Elimination Half-Life (t1/2) of Warfarin | Terminal phase elimination half-life (t1/2) of Warfarin | Up to 71 Days | 
| Maximum Observed Plasma Concentration (Cmax) of Omeprazole | Maximum observed plasma concentration (Cmax) of Omeprazole | Up to 71 Days | 
| Time to Maximum Observed Plasma Concentration (Tmax) of Omeprazole | Time to maximum plasma concentration (Tmax) of Omeprazole | Up to 71 Days | 
| Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Omeprazole | Area Under the Plasma Concentration-time Curve (AUC) from time 0 to time of the last measurable concentration | Up to 71 Days | 
| AUC From Time 0 to Infinity (AUCinf) of Omeprazole | Area Under the Plasma Concentration-time Curve (AUC) from time 0 to infinity | Up to 71 Days | 
| Terminal Phase Elimination Rate Constant (β) of Omeprazole | Terminal phase elimination rate constant (β) for Omeprazole | Up to 71 Days | 
| Terminal Phase Elimination Half-Life (t1/2) of Omeprazole | Terminal phase elimination half-life (t1/2) of Omeprazole | Up to 71 Days | 
| Maximum Observed Plasma Concentration (Cmax) of Metoprolol | Maximum observed plasma concentration (Cmax) of Metoprolol | Up to 71 Days | 
| Time to Maximum Observed Plasma Concentration (Tmax) of Metoprolol | Time to maximum plasma concentration (Tmax) of Metoprolol | Up to 71 Days | 
| Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Metoprolol | Area Under the Plasma Concentration-time Curve (AUC) from time 0 to time of the last measurable concentration | Up to 71 Days | 
| AUC From Time 0 to Infinity (AUCinf) of Metoprolol | Area Under the Plasma Concentration-time Curve (AUC) from time 0 to infinity | Up to 71 Days | 
| Terminal Phase Elimination Rate Constant (β) of Metoprolol | Terminal phase elimination rate constant (β) for Metoprolol | Up to 71 Days | 
| Terminal Phase Elimination Half-Life (t1/2) of Metoprolol | Terminal phase elimination half-life (t1/2) of Metoprolol | Up to 71 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative Colitis (UC), Crohn's Disease, Risankizumab, SKYRIZI, ABBV-066, Cytochrome P450