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

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

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.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease; Ulcerative Colitis (UC)
• Intervention / Treatment: Drug: Risankizumab; Drug: Cytochrome P450 (CYP) Substrates

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charite Research Organisation GmbH /ID# 218646
• Israel
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 223959
• United States
  • California
    • Coronado, California, United States, 92118-1408
      • Southern California Res. Ctr. /ID# 216257
  • Florida
    • DeLand, Florida, United States, 32720
      • University Clinical Research /ID# 216823
    • Margate, Florida, United States, 33063-5737
      • Atlantic Medical Research Group /ID# 227465
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc /ID# 216277

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cytochrome P450 (CYP) + Risankizumab; 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; Intravenous (IV) infusion; Other Names: ABBV-066; SKYRIZI; Drug: Cytochrome P450 (CYP) Substrates; Tablet: Oral; CYP Substrates: midazolam, caffeine, warfarin, vitamin K, omeprazole and metoprolol

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

Helpful Links

• This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2020
• Primary Completion (Actual): October 14, 2022
• Study Completion (Actual): October 14, 2022

Study Registration Dates

• First Submitted: February 3, 2020
• First Submitted That Met QC Criteria: February 3, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): October 24, 2022
• Last Update Submitted That Met QC Criteria: October 20, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Ulcerative Colitis (UC); Crohn's Disease; Cytochrome P450; Risankizumab; ABBV-066; SKYRIZI
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Crohn Disease; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: M19-974; 2019-003684-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes