Clinical trial NCT02772601: This Study Tests the Effect of Risankizumab on the Metabolism in the Liver of Five Additional Drugs to Study Possible Drug Interactions in Patients With Psoriasis With or Without Psoriatic Arthritis
Official title: The Effect of Multiple Subcutaneous Doses of Risankizumab on the Single Dose Pharmacokinetics of Cytochrome P450 Substrates (Caffeine, Warfarin, Omeprazole, Metoprolol and Midazolam) Administered Orally in an Open-label, One-sequence Trial in Patients With Plaque Psoriasis With or Without Concomitant Psoriatic Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Psoriasis
Keywords: ABBV-066
BI 655066
risankizumab
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Boehringer Ingelheim
First posted: 2016-05-13
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess the influence of risankizumab on kinetics of cytochrome P450 (CYP) probe drugs as a means of predicting drug-drug interactions.


Eligibility criteria: Inclusion criteria:

* Signed and dated written informed consent in accordance with GCP (Good Clinical Practice) and local legislation prior to admission to the trial and prior to any trial related procedure.
* Age 18 years to 75 years at screening
* Body mass index of 18.5 to 40.0 kg/m2 and within the weight range of 50 to 148 kg
* Male or female patients.
* If female, subject must be either postmenopausal, defined as:

  * Age \> 55 years with no menses for 12 or more months without an alternative medical cause.
  * Age \< 55 years with no menses for 12 or more months without an alternative medical cause AND an FSH level \> 40 IU/L.

OR

* Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
* Females must have negative results for pregnancy tests performed:

  * at Screening on a urine sample obtained within 30 days prior to initial study drug administration, and
  * prior to initial dosing on a serum sample obtained at the start of confinement
* Women of Childbearing Potential (WOCBP) must practice at least one of the following methods of birth control, on Study Day 1 (or earlier) through at least 140 days after the last dose of study drug.

  * Combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) associated with the inhibition of ovulation, initiated at least 1 month prior to Study Day 1.
  * Progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation, initiated at least 1 month prior to Study Day 1.
  * Bilateral tubal occlusion/ligation.
  * Vasectomized partner(s), provided the vasectomized partner has received medical assessment of the surgical success and is the sole sexual partner of the WOCBP trial participant.
  * Intrauterine device (IUD).
  * Intrauterine hormone-releasing system (IUS).
  * True abstinence: Refraining from heterosexual intercourse-when this is in line with the preferred and usual lifestyle of the subject. (Note: Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable).
* Further inclusion criteria apply.

Exclusion criteria:

* Patients with

  * non-plaque forms of psoriasis (including guttate, erythrodermic, or pustular)
  * current drug-induced psoriasis (including an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium)
  * active ongoing inflammatory diseases other than psoriasis that might confound trial evaluations according to investigator's judgment
* Participation in another trial with an investigational drug or device within 4 weeks or 5 half-lives (whichever is greater) prior to screening. Observational study is permitted.
* Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the study, as assessed by the investigator
* Major surgery performed within 12 weeks prior to screening or planned within 10 months after screening (e.g. hip replacement, aneurysma removal, stomach ligation)
* Active systemic infections during the last 2 weeks (exception: common cold) prior to screening
* Chronic or relevant acute infections including HIV (Human Immunodeficiency Virus), viral hepatitis and (or) tuberculosis or evidence of tuberculosis infection as defined by a positive QuantiFERON TB (tuberculosis) test within 2 months prior to or during screening. Patients with a positive QuantiFERON TB test may participate in the study if further work up including a chest X-ray (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active tuberculosis and initiation of treatment during the conduct of this study is not needed. If presence of latent tuberculosis is established, then treatment according to local country guidelines must have been initiated and completed prior to study initiation.
* Active HBV (Hepatitis B Virus) and HCV (Hepatitis C Virus), defined as:

  * HBV: hepatitis B surface antigen (HBs Ag) positive (+),HBcAb positive or detected sensitivity on the HBV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) qualitative test for Hepatitis B core antibody (HBc Ab);
  * HCV: HCV ribonucleic acid (RNA) detectable in any subject with anti-HCV antibody (HCV Ab).
* Positive screen for drugs of abuse, alcohol or cotinine at Screening.
* Use of known inhibitors or inducers of CYP1A2, 2C9, 2C19, 2D6 or 3A4, including dietary supplements or herbal products containing St. John's wort (Hypericum perforatum) or other known CYP inducers or inhibitors within 30 days or 5 half-lives, whichever is greater prior to study CYP cocktail probe drug administration.
* Use of grapefruits, Seville oranges (sour or bitter oranges), starfruit and their juices, quinine, tonic water, dietary/herbal supplements and inhibitors of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and organic anion-transporting polypeptide 1B1/1B3 (OATP1B1/1B3) transporters within 14 days or 5 half-lives of the respective medication before CYP cocktail probe drug administration.
* Current smokers of nicotine containing products, including those who quit smoking less than 30 days prior to CYP cocktail probe drug administration.
* Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix
* Plans for administration of live vaccines during the study period or within 6 weeks prior to screening
* Further exclusion criteria apply.

Primary outcomes:
measure: AUC0 - tz (area under the concentration-time curve) of caffeine with risankizumab in plasma over time interval from 0 to last quantifiable data point
timeFrame: Day 98-101
measure: AUC0 - tz (area under the concentration-time curve) of caffeine without risankizumab in plasma over time interval from 0 to last quantifiable data point
timeFrame: Day 1-3
measure: AUC0 - tz (area under the concentration-time curve) of warfarin with risankizumab in plasma over time interval from 0 to last quantifiable data point
timeFrame: Day 98 - 105
measure: AUC0 - tz (area under the concentration-time curve) of warfarin without risankizumab in plasma over time interval from 0 to last quantifiable data point
timeFrame: Day 1-8
measure: AUC0 - tz (area under the concentration-time curve) of omeprazole with risankizumab in plasma over time interval from 0 to last quantifiable data point
timeFrame: Day 98 - 100
measure: AUC0 - tz (area under the concentration-time curve) of omeprazole without risankizumab in plasma over time interval from 0 to last quantifiable data point
timeFrame: Day 1-2
measure: AUC0 - tz (area under the concentration-time curve) of metoprolol with risankizumab in plasma over time interval from 0 to last quantifiable data point
timeFrame: Day 98 -100
measure: AUC0 - tz (area under the concentration-time curve) of metoprolol without risankizumab in plasma over time interval from 0 to last quantifiable data point
timeFrame: Day 1-3
measure: AUC0 - tz (area under the concentration-time curve) of midazolam with risankizumab in plasma over time interval from 0 to last quantifiable data point
timeFrame: Day 98 - 99
measure: AUC0 - tz (area under the concentration-time curve) of midazolam without risankizumab in plasma over time interval from 0 to last quantifiable data point
timeFrame: Day 1-2
measure: Cmax (maximum measured concentration) of the analyte omeprazole without risankizumab in plasma
timeFrame: Day 1
measure: Cmax (maximum measured concentration) of the analyte metoprolol with risankizumab in plasma
timeFrame: Day 98
measure: Cmax (maximum measured concentration) of the analyte metoprolol without risankizumab in plasma
timeFrame: Day 1
measure: Cmax (maximum measured concentration) of the analyte midazolam with risankizumab in plasma
timeFrame: Day 98
measure: Cmax (maximum measured concentration) of the analyte midazolam without risankizumab in plasma
timeFrame: Day 1
measure: Cmax (maximum measured concentration) of the analyte caffeine with risankizumab in plasma
timeFrame: Day 98
measure: Cmax (maximum measured concentration) of the analyte caffeine without risankizumab in plasma
timeFrame: Day 1
measure: Cmax (maximum measured concentration) of the analyte warfarin with risankizumab in plasma
timeFrame: Day 98
measure: Cmax (maximum measured concentration) of the analyte warfarin without risankizumab in plasma
timeFrame: Day 1
measure: Cmax (maximum measured concentration) of the analyte omeprazole with risankizumab in plasma
timeFrame: Day 98
Secondary outcomes:
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Boehringer Ingelheim Investigational Site
Study officials:
affiliation: AbbVie
name: Lawrence Mcnamee
role: STUDY_DIRECTOR
References:
citation: Khatri A, Cheng L, Camez A, Ignatenko S, Pang Y, Othman AA. Lack of Effect of 12-Week Treatment with Risankizumab on the Pharmacokinetics of Cytochrome P450 Probe Substrates in Patients with Moderate to Severe Chronic Plaque Psoriasis. Clin Pharmacokinet. 2019 Jun;58(6):805-814. doi: 10.1007/s40262-018-0730-x.