Clinical trial NCT04254783: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ulcerative Colitis (UC)
Crohn's Disease
Keywords: Ulcerative Colitis (UC)
Crohn's Disease
Risankizumab
SKYRIZI
ABBV-066
Cytochrome P450
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2020-02-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Midazolam
timeFrame: Up to 71 Days
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Midazolam
timeFrame: Up to 71 Days
measure: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Midazolam
timeFrame: Up to 71 Days
measure: AUC From Time 0 to Infinity (AUCinf) of Midazolam
timeFrame: Up to 71 Days
measure: Terminal Phase Elimination Rate Constant (β) of Midazolam
timeFrame: Up to 71 Days
measure: Terminal Phase Elimination Half-Life (t1/2) of Midazolam
timeFrame: Up to 71 Days
measure: Maximum Observed Plasma Concentration (Cmax) of Caffeine
timeFrame: Up to 71 Days
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Caffeine
timeFrame: Up to 71 Days
measure: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Caffeine
timeFrame: Up to 71 Days
measure: AUC From Time 0 to Infinity (AUCinf) of Caffeine
timeFrame: Up to 71 Days
measure: Terminal Phase Elimination Rate Constant (β) of Caffeine
timeFrame: Up to 71 Days
measure: Terminal Phase Elimination Half-Life (t1/2) of Caffeine
timeFrame: Up to 71 Days
measure: Maximum Observed Plasma Concentration (Cmax) of Warfarin
timeFrame: Up to 71 Days
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Warfarin
timeFrame: Up to 71 Days
measure: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Warfarin
timeFrame: Up to 71 Days
measure: AUC From Time 0 to Infinity (AUCinf) of Warfarin
timeFrame: Up to 71 Days
measure: Terminal Phase Elimination Rate Constant (β) of Warfarin
timeFrame: Up to 71 Days
measure: Terminal Phase Elimination Half-Life (t1/2) of Warfarin
timeFrame: Up to 71 Days
measure: Maximum Observed Plasma Concentration (Cmax) of Omeprazole
timeFrame: Up to 71 Days
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Omeprazole
timeFrame: Up to 71 Days
measure: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Omeprazole
timeFrame: Up to 71 Days
measure: AUC From Time 0 to Infinity (AUCinf) of Omeprazole
timeFrame: Up to 71 Days
measure: Terminal Phase Elimination Rate Constant (β) of Omeprazole
timeFrame: Up to 71 Days
measure: Terminal Phase Elimination Half-Life (t1/2) of Omeprazole
timeFrame: Up to 71 Days
measure: Maximum Observed Plasma Concentration (Cmax) of Metoprolol
timeFrame: Up to 71 Days
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Metoprolol
timeFrame: Up to 71 Days
measure: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Metoprolol
timeFrame: Up to 71 Days
measure: AUC From Time 0 to Infinity (AUCinf) of Metoprolol
timeFrame: Up to 71 Days
measure: Terminal Phase Elimination Rate Constant (β) of Metoprolol
timeFrame: Up to 71 Days
measure: Terminal Phase Elimination Half-Life (t1/2) of Metoprolol
timeFrame: Up to 71 Days
Secondary outcomes:
Other outcomes:
Locations:
city: Coronado
country: United States
facility: Southern California Res. Ctr. /ID# 216257
state: California
city: DeLand
country: United States
facility: University Clinical Research /ID# 216823
state: Florida
city: Margate
country: United States
facility: Atlantic Medical Research Group /ID# 227465
state: Florida
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc /ID# 216277
state: Texas
city: Berlin
country: Germany
facility: Charite Research Organisation GmbH /ID# 218646
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 223959
state: Tel-Aviv
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: