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

Crohn's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04254783
• Other study ID #: M19-974
• Secondary ID: 2019-003684-22
• Status: Completed
• Phase: Phase 1
• Start date: May 27, 2020
• Est. completion date: October 14, 2022

Study information

• Verified date: October 2022
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 14, 2022
• Est. primary completion date: October 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Crohn Disease
• Crohn's Disease
• Ulcer
• Ulcerative Colitis (UC)

Intervention

Drug:
• Risankizumab
Intravenous (IV) infusion
• Cytochrome P450 (CYP) Substrates
Tablet: Oral; CYP Substrates: midazolam, caffeine, warfarin, vitamin K, omeprazole and metoprolol

Locations

Country	Name	City	State
Germany	Charite Research Organisation GmbH /ID# 218646	Berlin
Israel	The Chaim Sheba Medical Center /ID# 223959	Ramat Gan	Tel-Aviv
United States	Southern California Res. Ctr. /ID# 216257	Coronado	California
United States	University Clinical Research /ID# 216823	DeLand	Florida
United States	Atlantic Medical Research Group /ID# 227465	Margate	Florida
United States	Clinical Trials of Texas, Inc /ID# 216277	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Germany,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of Midazolam	Maximum observed plasma concentration (Cmax) of Midazolam	Up to 71 Days
Primary	Time to Maximum Observed Plasma Concentration (Tmax) of Midazolam	Time to maximum plasma concentration (Tmax) of Midazolam	Up to 71 Days
Primary	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
Primary	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
Primary	Terminal Phase Elimination Rate Constant (ß) of Midazolam	Terminal phase elimination rate constant (ß) for Midazolam	Up to 71 Days
Primary	Terminal Phase Elimination Half-Life (t1/2) of Midazolam	Terminal phase elimination half-life (t1/2) of Midazolam	Up to 71 Days
Primary	Maximum Observed Plasma Concentration (Cmax) of Caffeine	Maximum observed plasma concentration (Cmax) of Caffeine	Up to 71 Days
Primary	Time to Maximum Observed Plasma Concentration (Tmax) of Caffeine	Time to maximum plasma concentration (Tmax) of Caffeine	Up to 71 Days
Primary	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
Primary	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
Primary	Terminal Phase Elimination Rate Constant (ß) of Caffeine	Terminal phase elimination rate constant (ß) for Caffeine	Up to 71 Days
Primary	Terminal Phase Elimination Half-Life (t1/2) of Caffeine	Terminal phase elimination half-life (t1/2) of Caffeine	Up to 71 Days
Primary	Maximum Observed Plasma Concentration (Cmax) of Warfarin	Maximum observed plasma concentration (Cmax) of Warfarin	Up to 71 Days
Primary	Time to Maximum Observed Plasma Concentration (Tmax) of Warfarin	Time to maximum plasma concentration (Tmax) of Warfarin	Up to 71 Days
Primary	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
Primary	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
Primary	Terminal Phase Elimination Rate Constant (ß) of Warfarin	Terminal phase elimination rate constant (ß) for Warfarin	Up to 71 Days
Primary	Terminal Phase Elimination Half-Life (t1/2) of Warfarin	Terminal phase elimination half-life (t1/2) of Warfarin	Up to 71 Days
Primary	Maximum Observed Plasma Concentration (Cmax) of Omeprazole	Maximum observed plasma concentration (Cmax) of Omeprazole	Up to 71 Days
Primary	Time to Maximum Observed Plasma Concentration (Tmax) of Omeprazole	Time to maximum plasma concentration (Tmax) of Omeprazole	Up to 71 Days
Primary	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
Primary	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
Primary	Terminal Phase Elimination Rate Constant (ß) of Omeprazole	Terminal phase elimination rate constant (ß) for Omeprazole	Up to 71 Days
Primary	Terminal Phase Elimination Half-Life (t1/2) of Omeprazole	Terminal phase elimination half-life (t1/2) of Omeprazole	Up to 71 Days
Primary	Maximum Observed Plasma Concentration (Cmax) of Metoprolol	Maximum observed plasma concentration (Cmax) of Metoprolol	Up to 71 Days
Primary	Time to Maximum Observed Plasma Concentration (Tmax) of Metoprolol	Time to maximum plasma concentration (Tmax) of Metoprolol	Up to 71 Days
Primary	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
Primary	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
Primary	Terminal Phase Elimination Rate Constant (ß) of Metoprolol	Terminal phase elimination rate constant (ß) for Metoprolol	Up to 71 Days
Primary	Terminal Phase Elimination Half-Life (t1/2) of Metoprolol	Terminal phase elimination half-life (t1/2) of Metoprolol	Up to 71 Days

External Links

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